PT  - JOURNAL ARTICLE
AU  - EISUKE KURIHARA
AU  - KAZUHIKO SHIEN
AU  - HIDEJIRO TORIGOE
AU  - TATSUAKI TAKEDA
AU  - YUTA TAKAHASHI
AU  - YUSUKE OGOSHI
AU  - TAKAHIRO YOSHIOKA
AU  - KEI NAMBA
AU  - HIROKI SATO
AU  - KEN SUZAWA
AU  - HIROMASA YAMAMOTO
AU  - JUNICHI SOH
AU  - MIKIO OKAZAKI
AU  - TADAHIKO SHIEN
AU  - SHUTA TOMIDA
AU  - SHINICHI TOYOOKA
TI  - Ganetespib in Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor-resistant Non-small Cell Lung Cancer
AID  - 10.21873/anticanres.13283
DP  - 2019 Apr 01
TA  - Anticancer Research
PG  - 1767--1775
VI  - 39
IP  - 4
4099  - http://ar.iiarjournals.org/content/39/4/1767.short
4100  - http://ar.iiarjournals.org/content/39/4/1767.full
SO  - Anticancer Res2019 Apr 01; 39
AB  - Background: The 90-kDa heat-shock protein (HSP90) is a chaperone protein expressed at high levels in cancer cells and is involved in the folding or stabilization of several client proteins, including epidermal growth factor receptor (EGFR). Ganetespib is a second-generation HSP90 inhibitor with a potent antitumor effect against various cancer types. Materials and Methods: This study examined the antitumor effect of ganetespib in EGFR-mutant non-small cell lung cancer (NSCLC) cells and experimentally established EGFR-tyrosine kinase inhibitor (TKI)-resistant cells harboring various resistance mechanisms, including EGFR T790M mutation, met proto-oncogene amplification, and epithelial–mesenchymal transition. Results: Ganetespib showed a potent antitumor effect at low concentrations, suppressing EGFR-related downstream pathway molecules and inducing cleavage of poly ADP-ribose polymerase in all examined EGFR-TKI-resistant cell lines in vitro. Ganetespib also inhibited in vivo tumor growth in resistant cells harboring EGFR T790M. Conclusion: Ganetespib might be a promising therapeutic option for the treatment of patients with EGFR-TKI-resistant NSCLC.